I.O.S.& COLEMAN Srl, Naples, Italy.
Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Naples, Italy.
Reprod Toxicol. 2017 Oct;73:105-127. doi: 10.1016/j.reprotox.2017.07.021. Epub 2017 Aug 1.
Cadmium is an environmental pollutant known as endocrine disruptor. Testis is particularly susceptible to cadmium, and testis injury occurs at high but even low levels of exposure. Cadmium reproductive toxicity is mediated by multiple mechanisms, including structural damage to testis vasculature and blood-testis barrier, inflammation, cytotoxicity on Sertoli and Leydig cells, oxidative stress mainly by means of mimicry and interference with essential ions, apoptosis, interference with selected signaling pathways and epigenetic regulation of genes involved in the regulation of reproductive function, and disturbance of the hypothalamus-pituitary-gonadal axis. The current review outlines epidemiological observational findings from environmental and occupational exposure in humans, and reports experimental studies in humans and animals. Lastly, a focus on the pathogenetic mechanisms of cadmium toxicity and on the specific mechanisms of cadmium sensitivity and resistance, particularly assessed in animal models, is included. Despite convincing experimental findings in animals and supporting evidences in humans identifying cadmium as reproductive toxicant, observational findings are controversial, suffering from heterogeneity of study design and pattern of exposure, and from co-exposure to multiple pollutants.
镉是一种环境污染物,被称为内分泌干扰物。睾丸对镉特别敏感,即使在低水平暴露时也会发生睾丸损伤。镉的生殖毒性是通过多种机制介导的,包括对睾丸血管和血睾屏障的结构损伤、炎症、对支持细胞和间质细胞的细胞毒性、主要通过模拟和干扰必需离子的氧化应激、细胞凋亡、干扰选定的信号通路以及参与调节生殖功能的基因的表观遗传调控,以及下丘脑-垂体-性腺轴的紊乱。本综述概述了人类环境和职业暴露的流行病学观察结果,并报告了人类和动物的实验研究。最后,重点介绍了镉毒性的发病机制以及镉敏感性和抗性的特定机制,特别是在动物模型中进行了评估。尽管动物实验中存在令人信服的发现,并在人类中提供了支持证据,将镉确定为生殖毒物,但观察性研究结果存在争议,受到研究设计和暴露模式的异质性以及多种污染物共同暴露的影响。